Summary: Williams et al. performed a multicenter prospective observational study that included 1418 children hospitalized with radiographically confirmed pneumonia to compare the effectiveness of those who received β-lactam monotherapy vs β-lactam plus macrolide combination therapy. They found no significant differences between the two treatment regimens in regard to length of hospitalization, ICU admissions, reported recovery at follow-up or percentage of rehospitalizations. Furthermore, the authors also performed subgroup analyses across 4 groups in whom macrolide combination therapy might offer the most benefit (age > 5 years, atypical bacteria detected, admitted to the ICU, and children with acute wheezing) and found no significant differences between group members who received β-lactam monotherapy and those who received β-lactam plus macrolide combination therapy.

Key Strengths: Strengths of the study include that it was nested within a larger pneumonia etiology study that used a strict definition of clinical and radiographically confirmed pneumonia and detailed microbiological assessments. Furthermore, they made significant efforts to minimize possible confounding by including indicators of illness severity and radiographic patterns as covariates in their matched cohort. Limitations: Limitations include it was a non-randomized observational study without a placebo group. 44% of the patients in each treatment group had wheezing, so it is possible this reflects a cohort of patients with bronchiolitis or asthma as opposed to bacterial pneumonia. In addition, since >70% of children had a virus detected, a difference may not have been observed between the groups since antibiotics may not be needed at all in the majority of children with image findings of pneumonia.

Major takeaway message: In a large cohort of children with community acquired pneumonia, the addition of a macrolide antibiotic to empiric β-lactam therapy did not show any benefit across a variety of outcome measures even when looking at groups of patients who traditionally were believed to receive the most benefit from the addition of macrolide therapy.

Describe how this article should impact our practice: This study adds significantly to the growing body of literature that the addition of macrolide therapy for community acquired pneumonia may not benefit the majority of patients we typically prescribe it for and thus should make us question its routine use for empirical treatment. We should continue this conversation with the goal of reducing unnecessary antibiotic treatments to improve antibiotic stewardship, reduce risk of unnecessary adverse side effects, and save cost.